A cancer vaccine-mediated postoperative immunotherapy for recurrent and metastatic tumors

Tingting Wang, Dangge Wang, Haijun Yu, Bing Feng, Fangyuan Zhou, Hanwu Zhang, Lei Zhou, Shi Jiao, Yaping Li

Nature Communications · 2018 · 395 citations · 30 references

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TL;DR

Vaccines that elicit durable antitumor immunity hold promise for postoperative cancer therapy, yet achieving simultaneous tumor‑specific immunity and overcoming immune resistance remains challenging. We present a personalized cancer vaccine (PVAX) for postsurgical immunotherapy. PVAX is created by encapsulating JQ1 and indocyanine green–loaded tumor cells in a hydrogel matrix, and NIR light triggers antigen release while JQ1 blocks PD‑L1, together driving the therapeutic effect. PVAX activation by 808 nm NIR laser markedly suppresses tumor relapse by maturing dendritic cells and recruiting cytotoxic T cells, and autologous tumor‑cell PVAX induces patient‑specific memory responses that prevent recurrence and metastasis, offering new insights for postoperative immunotherapy.

Abstract

Vaccines to induce effective and sustained antitumor immunity have great potential for postoperative cancer therapy. However, a robust cancer vaccine simultaneously eliciting tumor-specific immunity and abolishing immune resistance continues to be a challenge. Here we present a personalized cancer vaccine (PVAX) for postsurgical immunotherapy. PVAX is developed by encapsulating JQ1 (a BRD4 inhibitor) and indocyanine green (ICG) co-loaded tumor cells with a hydrogel matrix. Activation of PVAX by 808 nm NIR laser irradiation significantly inhibits the tumor relapse by promoting the maturation of dendritic cells and eliciting tumor infiltration of cytotoxic T lymphocytes. A mechanical study reveals that NIR light-triggered antigen release and JQ1-mediated PD-L1 checkpoint blockade cumulatively contribute to the satisfied therapeutic effect. Furthermore, PVAX prepared from the autologous tumor cells induces patient-specific memory immune response to prevent tumor recurrence and metastasis. The PVAX model might provide novel insights for postoperative immunotherapy.

References

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